This career transition award will provide the necessary resources to assess the role of the complement system in asthma. Given that asthma is a major world-wide health problem, this research proposal will attempt to delineate the overall contribution of the complement system in the pathogenesis of asthma and, specifically, investigate the complement-mediated regulation of cell types that control asthma-associated responses. This hypothesis will be addressed through the use of an Aspergillus fumigatus animal model of pulmonary allergy utilizing mice that are deficient in the central component of the complement system C3 and the complement anaphylatoxin receptors which can contribute to airway hyperreactivity and inflammation. Furthermore, since Th2 and IgE responses are an important component of pulmonary allergy, and the role of complement has not been evaluated in regards to this facet, specific attention will be given to the ability of the complement system to regulate these asthma-associated responses. Collectively, this study will assess the expression, function, and participation of the complement system in airway inflammation during the course of asthma by evaluating asthma-associated responses such as airway hyperresponsiveness, lung eosinophilia, mucus hypersecretion, and Th2 and IgE responses in complement deficient and wild type animals. Moreover, results generated from this proposal will provide valuable insight into the contribution of the complement system in T cell regulation and allergy as well as pulmonary host defense and disease.